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  • [Discriminative stimulus properties of phenazepam and lorazepam: specificity and role of GABA A receptors].

[Discriminative stimulus properties of phenazepam and lorazepam: specificity and role of GABA A receptors].

Eksperimental'naia i klinicheskaia farmakologiia (2008-03-28)
T S Kalinina, T A Voronina, E V Petrianina
ABSTRACT

Rats were trained to distinguish the injections of phenazepam (PZ, 2 mg/kg, i.p.) and lorazepam (LZ, 2 mg/kg, i.p.) from saline in the same dose in the two-lever liquid-reinforced operant drug-discrimination (DD) paradigm experiment. A very similar level of stimulus control was obtained in both PZ- and LZ-trained animals throughout the 14 and 19-day duration of the study, respectively, the accuracy of the appropriate lever responses being no less than 80% in both cases. The principal similarity of the dynamics of PZ-saline and LZ-saline stimulus discrimination in different operant behavior schedules, their generalization profiles and the results of cross-substitution testing are indicative of the identity of the interoceptive DD properties of PZ and LZ. The results of cross-substitution tests with phenobarbital (40-100 mg/kg, i.p.), pentobarbital (10 mg/kg, i.p.), muscimol (1 mg/kg, i.p.), calcium valproate (20 mg/kg, i.p.), and pregnanolone (2 mg/kg, i.p.) as well as the tests for antagonism with bicuculline (10 mg/kg, i.p.) and picrotoxin (2 mg/kg, i.p.) showed that the DD properties of LZ strongly depend on the functional activity of GABA receptors and to a much lesser extent on the picrotoxin-binding receptor component of the GABA-receptor complex, which is additional evidence for the principal similarity of the interoceptive effects of PZ and LZ.